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Non-monotonic dose-response of di-(2-ethylhexyl) phthalate isolated from Penicillium citrinum XT6 on adipogenesis and expression of PPARγ and GLUT4 in 3T3-L1 adipocytes

  • Fitra Fauziah ORCID logo , Hirowati Ali ORCID logo , Cimi Ilmiawati ORCID logo , Eko Fuji Ariyanto ORCID logo , Dwi Dinni Aulia Bakhtra ORCID logo , Deslina Setria Mita , Nova Syafni ORCID logo and Dian Handayani ORCID logo EMAIL logo
Published/Copyright: July 24, 2023
Journal of Complementary and Integrative Medicine
From the journal Journal of Complementary and Integrative Medicine Volume 20 Issue 4

Abstract

Objectives

Adipogenesis is the fat cell formation process regulated by peroxisome proliferator-activated receptors (PPARγ). The insulin-responsive glucose transporter 4 (GLUT4) has a major role in glucose uptake and metabolism in insulin target tissues (i.e., adipose and muscle cells). The interplay between PPARγ and GLUT4 is essential for proper glucose homeostasis. This study aimed to isolate, elucidate, and investigate the effect of an isolated compound from Penicillium citrinum XT6 on adipogenesis, PPARγ, and GLUT4 expression in 3T3-L1 adipocytes.

Methods

The isolated compound was determined by analyzing spectroscopic data (LC-MS, FT-IR, Spectrophotometry UV–Vis, and NMR). The adipogenesis activity of the isolated compound in 3T3-L1 cells was determined by the Oil Red O staining method. RT-PCR was used to analyze the gene expression of PPARγ and GLUT4.

Results

Di-(2-ethylhexyl)-phthalate (DEHP) was the isolated compound from P.citrinum XT6. The results revealed adipogenesis stimulation and inhibition, as well as PPARγ and GLUT4 expressions.

Conclusions

DEHP showed a non-monotonic dose-response (NMDR) effect on adipogenesis and PPARγ and GLUT4 expression. It is the first study that reveals DEHP’s NMDR effects on lipid and glucose metabolism in adipocytes.

Keywords: adipogenesis; DEHP; GLUT4 ; non-monotonic dose-response; Penicillium citrinum ; PPARγ
Corresponding author: Dian Handayani, Laboratory of Sumatran Biota/Faculty of Pharmacy, Universitas Andalas, Padang 25163, Indonesia, E-mail:

Funding source: Doctoral Dissertation Grant Program from The Ministry of Research and Technology

Award Identifier / Grant number: 021/E4.1/AK.04.PT/2021

Acknowledgments

We want to thank the Laboratory of the School of Pharmaceutical Sciences Padang (STIFARM Padang), West Sumatera, Indonesia, and the Cell Culture and Cytogenetics Laboratory, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia for contributing to this study.

  1. Research funding: The Ministry of Research and Technology funded this project through the “Doctoral Dissertation Grant Program” on “Single Basic Scheme Research and Coaching/Capability In Higher Education” No. 021/E4.1/AK.04.PT/2021.

  2. Author contributions: Conceptualization and methodology, F.F., H.A., C.I., E.F.A., D.H.; software, F.F.; validation H.A., C.I., E.F.A., D.H.; formal analysis F.F., N.S.; investigation F.F., D.S.M., D.D.A.B.; resources F.F., D.H.; data curation F.F., D.H.; writing-original draft preparation F.F.; writing-review and editing F.F., H.A., C.I., E.F.A., N.S., D.H.; visualization F.F.; supervision H.A., C.I., D.H.; project administration F.F., D.S.M.; funding acquisition D.H. All authors have read and agreed to the published version of the manuscript.

  3. Competing interests: The authors states no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jcim-2023-0137).

Received: 2023-05-18
Accepted: 2023-07-01
Published Online: 2023-07-24

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jcim-2023-0137
Keywords for this article
adipogenesis; DEHP; GLUT4; non-monotonic dose-response; Penicillium citrinum; PPARγ

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Plants with potential anti-ulcerogenic activity and possible mechanism of actions based on their phyto-constitutional profile
  4. Ayurvedic medicine for the treatment of chronic rhinosinusitis: a systematic review of randomized and non-randomized trials
  5. The roles of HDAC with IMPDH and mTOR with JAK as future targets in the treatment of rheumatoid arthritis with combination therapy
  6. Research Articles
  7. Alterations in expression of α1-adrenergic receptors possibly are involved in prevention of age-associated apoptosis in rat hippocampus by treadmill exercise
  8. A solid lipid particle formulation of long pepper extract reduces pain and astrocyte activation in a rat model of neuropathic pain
  9. Modulation of glucose metabolism-related genes in diabetic rats treated with herbal synthetic anti-diabetic compound (α-HSA): insights from transcriptomic profiling
  10. Gastroprotective and ulcer healing effects of Nauclea pobeguinii (Rubiaceae) on experimentally induced gastric ulcers in male Wistar rats
  11. Blood pressure lowering effects of Vernonia amygdalina Del. Aqueous fraction on hypertensive Wistar Kyoto rats
  12. Oleaster oil (Olea europaea sylvestris) effects on the efficiency of the reproductive system of diet-induced obese male Wistar rats
  13. Antidiarrheal activity of Bridelia ferruginea bark methanolic extract involves modulation ATPases in mice and inhibition of muscarinic acetylcholine receptor (M3) and prostaglandin E2 receptor 3 (EP3) in silico
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